All organisms, from bacteria to humans, need to recognize where they are, and respond accordingly. A pathogen must sense its location in the infectious cycle, then produce factors necessary for that site while repressing synthesis of inappropriate factors. This is particularly important for vector-borne pathogens such as the Lyme disease agent, Borrelia burgdorferi, which must not only infect two very different types of animals, but efficiently transmit back-and-forth between vertebrate hosts and arthropod vectors. The planned studies bring together two experts in B. burgdorferi genetics and an expert bioinformatician into an integrated, systems approach that will map the regulatory networks of B. burgdorferi. The results will yield significant insight on B. burgdorferi physiology, its ability t cause disease and, since disruption of key regulatory pathways can inhibit a pathogen's ability to cause infection, identify strategic targets for developing novel antibiotics. The substantial quantity of derived data will also be made publicly available through electronic databases, providing a treasury of valuable information that can be readily mined by the global research community.